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Mech Ageing Dev. 2019 Mar;178:33-40. doi: 10.1016/j.mad.2018.12.003. Epub 2019 Jan 10.

Klotho gene polymorphisms are associated with healthy aging and longevity: Evidence from a meta-analysis.

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Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address:


Klotho gene polymorphisms have been implicated in healthy aging, but inconsistences in findings from previous case-control studies have raised concerns regarding the associations between KLOTHO gene polymorphisms and susceptibility to aging-related diseases and longevity. Hence, this meta-analysis was performed. We assessed the associations between two polymorphisms (G-395 A/rs1207568 and F352 V/rs9536314) and five parameters (urolithiasis, cognitive impairment, cardiovascular disease, cancer, and longevity) by calculating pooled odds ratios with 95% confidence intervals. According to the pooled results, the G allele of the G-395 A polymorphism conferred a significantly higher risk of urolithiasis; G-395 A was related to the susceptibility to cardiovascular disease under allele, dominant, and recessive models. There was no significant association between the G-395 A polymorphism and cognitive impairment among the elderly. The F allele of the F352 V polymorphism protected against breast and ovarian cancer susceptibility. Interestingly, based on the results of the subgroup analysis, the F352 V polymorphism was associated with the overall risk of neoplasms in BRCA1 mutation carriers but not in BRCA2 mutation carriers. Moreover, the F allele played a protective role in determining human longevity. In conclusion, Klotho G-395 A polymorphisms were associated with urolithiasis and cardiovascular disease but not with cognitive impairment. Additionally, Klotho F352 V polymorphisms were associated with cancers and longevity.


Aging; Gene polymorphisms; Klotho; Meta-Analysis

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